Epidemiological, scientific and immune elements that affect the persistence of antiphospholipid antibodies in leprosy.
Antiphospholipid antibodies (aPL) are described in people with leprosy with out the scientific options of antiphospholipid antibody syndrome (APS), a situation involving thromboembolic phenomena. We’ve got described the persistence of those antibodies for over 5 years in sufferers with leprosy after particular remedy.To find out whether or not epidemiological, scientific and immunological elements performed a job within the long-term persistence of aPL antibodies in leprosy sufferers after multidrug remedy (MDT) had completed.
METHODS
The research pattern consisted of 38 sufferers with a analysis of leprosy being adopted up on the Dermatology and Venereology Outpatient Division on the Alfredo da Matta Basis (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Sufferers have been reassessed on common of 5 years after particular remedy for the illness (MDT) had been accomplished.
RESULTS
Persistence of aPL antibodies among the many 38 leprosy sufferers was 84% (32/38), and all had the IgM isotype. Imply age was 48.1 ± 15.9 years, and 23 (72.0%) have been male. The lepromatous kind (LL) of leprosy was the commonest (n = 16, 50%). Reactional episodes have been noticed in three sufferers (9.4%). Eighteen (47.37%) have been nonetheless taking treatment (prednisone and/or thalidomide).
Imply IgM ranges have been 64 U/mL for aCL and 62 U/mL for anti-β2GPI. Within the multivariate binary logistic regression the next variables confirmed a big affiliation: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL scientific presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We didn’t discover affiliation between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively).
No variations within the variables vascular thrombosis, being pregnant morbidity, diabetes, smoking and alcoholism have been discovered between aPL-positive and aPL-negative sufferers.Persistence of positivity for aPL antibodies was influenced by age, scientific presentation and bacterial index. Nonetheless, additional research are wanted to elucidate the explanation for this persistence, the position performed by aPL antibodies within the illness and the B cell lineages liable for era of those antibodies.
Description: Interleukin 4 (IL-4) is a pleiotropic cytokine produced by activated T cells, mast cells, and basophils. It was initially identified as a B cell differentiation factor (BCDF), as well as a B cell stimulatory factor (BSF1). IL-4 has since been shown to have multiple biological effects on hematopoietic and non-hematopoietic cells, including B and T cells, monocytes, macrophages, mast cells, myeloid and erythroid progenitors, fibroblasts, and endothelial cells. Rat, mouse and human IL-4 are species-specific in their activities.
Description: Interleukin 4 (IL-4) is a pleiotropic cytokine produced by activated T cells, mast cells, and basophils. It was initially identified as a B cell differentiation factor (BCDF), as well as a B cell stimulatory factor (BSF1). IL-4 has since been shown to have multiple biological effects on hematopoietic and non-hematopoietic cells, including B and T cells, monocytes, macrophages, mast cells, myeloid and erythroid progenitors, fibroblasts, and endothelial cells. Rat, mouse and human IL-4 are species-specific in their activities.
Description: Interleukin 4 (IL-4) is a pleiotropic cytokine produced by activated T cells, mast cells, and basophils. It was initially identified as a B cell differentiation factor (BCDF), as well as a B cell stimulatory factor (BSF1). IL-4 has since been shown to have multiple biological effects on hematopoietic and non-hematopoietic cells, including B and T cells, monocytes, macrophages, mast cells, myeloid and erythroid progenitors, fibroblasts, and endothelial cells. Rat, mouse and human IL-4 are species-specific in their activities.
Dissecting the molecular foundation of excessive viscosity of monospecific and bispecific IgG antibodies.
Some antibodies exhibit elevated viscosity at excessive concentrations, making them poorly fitted to therapeutic functions requiring administration by injection akin to subcutaneous or ocular supply. Right here we studied an anti-IL-13/IL-17 bispecific IgG4 antibody, which has anomalously excessive viscosity in comparison with its mum or dad monospecific antibodies.
The viscosity of the bispecific IgG4 in answer was decreased by solely ~30% within the presence of NaCl, suggesting electrostatic interactions are inadequate to completely clarify the drivers of viscosity. Intriguingly, addition of arginine-HCl diminished the viscosity of the bispecific IgG4 by ~50% to its mum or dad IgG degree.
These information counsel that past electrostatics, further varieties of interactions akin to cation-π and/or π-π might contribute to excessive viscosity extra considerably than beforehand understood. Molecular dynamics simulations of antibody fragments within the blended answer of free arginine and specific water have been performed to establish hotspots concerned in self-interactions.
Uncovered floor fragrant amino acids displayed an elevated variety of contacts with arginine. Mutagenesis of the vast majority of fragrant residues pinpointed by molecular dynamics simulations successfully decreased the answer’s viscosity when examined experimentally.
This mutational methodology to scale back the viscosity of a bispecific antibody was prolonged to a monospecific anti-GCGR IgG1 antibody with elevated viscosity. In all circumstances, level mutants have been readily recognized that each diminished viscosity and retained antigen-binding affinity.
These research show a brand new method to mitigate excessive viscosity of some antibodies by mutagenesis of surface-exposed fragrant residues on complementarity-determining areas that will facilitate some scientific functions.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF-1), 152 (PlGF-2), and 203 (PlGF-3) amino acids (aa) respectively. Only PlGF-2 contains a highly basic heparin-binding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF-2 has been identified. Mouse PlGF shares 60%, 92%, 62% and 59% aa identity with the appropriate isoform of human, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during human pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt-1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2-mediated angiogenesis. However, PlGF (especially human PlGF-1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF-2, like VEGF164/165, shows heparin-dependent binding of neuropilin (Npn)-1 and Npn-2 and can inhibit nerve growth cone collapse. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis. Circulating PlGF often correlates with tumor stage and aggressiveness, and therapeutic P lGF antibodies are being investigated to inhibit tumor growth and angiogenesis.
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF1, PlGF2 and PlGF3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF1, PlGF2 and PlGF3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF1, PlGF2 and PlGF3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF-1, PlGF-2 and PlGF-3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF-2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF-2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF1, PlGF2 and PlGF3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Mouse PlGF Recombinant Protein expressed in Baculovirus with His-tag. Sequence domain: 27-158aa. Application(s): SDS-PAGE. Endotoxin: < 1 EU per 1ug of protein (determined by LAL method).
Description: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of growth factors. PlGF and VEGF share primary structural as well as limited amino acid sequence homology with the A and B chains of PDGF. All eight cysteine residues involved in intra and interchain disulfides are conserved among these growth factors. As a result of alternative splicing, three PlGF RNAs encoding monomeric human PlGF1, PlGF2 and PlGF3 isoform precursors containing 149, 179 and 219 amino acid residues, respectively, have been described. In normal mouse tissues, only one mouse PlGF mRNA encoding the equivalent of human PlGF2 has been identified. Mouse PlGF shares 65% amino acid identity with human PlGF2. The gene for PlGF has been mapped to mouse chromosome 12 and human chromosome 14. PlGF binds with high affinity to Flt1, but not to Flk1/KDR.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF-1), 152 (PlGF-2), and 203 (PlGF-3) amino acids (aa) respectively. Only PlGF-2 contains a highly basic heparin-binding 21 aa insert at the C-terminus. In rat only one PlGF that is the equivalent of human PlGF-2 has been identified. Rat PlGF shares 60%, 92%, 62% and 59% aa identity with the appropriate isoform of human, mouse, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during human pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt-1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2-mediated angiogenesis. However, PlGF (especially human PlGF-1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF-2, like VEGF164/165, shows heparin-dependent binding of neuropilin (Npn)-1 and Npn-2 and can inhibit nerve growth cone collapse. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis. Circulating PlGF often correlates with tumor stage and aggressiveness, and therapeutic PlGF antibodies are being investigated to inhibit tumor growth and angiogenesis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta growth factor (PlGF) is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF1), 152 (PlGF2), and 203 (PlGF3) amino acids (aa) respectively. Only PlGF2 contains a highly basic heparinbinding 21 aa insert at the C-terminus. In the mouse, only one P lGF that is the equivalent of human PlGF2 has been identified. Human PlGF1 shares 56%, 55%, 74% and 95% aa identity with the appropriate isoform of mouse, rat, canine and equine PlGF. PlGF is mainly found as variably glycosylated, secreted, 55 - 60 kDa disulfide linked homodimers. Mammalian cells expressing PlGF include villous trophoblasts, decidual cells, erythroblasts, keratinocytes and some endothelial cells. Circulating PlGF increases during pregnancy, reaching a peak in mid-gestation; this increase is attenuated in preeclampsia. However, deletion of PlGF in the mouse does not affect development or reproduction. Postnatally, mice lacking PlGF show impaired angiogenesis in response to ischemia. PlGF binds and signals through VEGF R1/Flt1, but not VEGF R2/Flk-1/KDR, while VEGF binds both but signals only through the angiogenic receptor, VEGF R2. PlGF and VEGF therefore compete for binding to VEGF R1, allowing high PlGF to discourage VEGF/VEGF R1 binding and promote VEGF/VEGF R2mediated angiogenesis. However, PlGF (especially PlGF1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF2, but not PLGF-1, shows heparindependent binding of neuropilin (Npn)-1 and Npn2. PlGF induces monocyte activation, migration, and production of inflammatory cytokines and VEGF. These activities facilitate wound and bone fracture healing, but also contribute to inflammation in active sickle cell disease and atherosclerosis.
Description: Placenta Growth Factor-2 (PlGF-2), a 22 kDa protein consisting of 152 amino acid residues is produced as a homodimer. PlGF is a polypeptide growth factor and a member of the platelet-derived growth factor family but more related to vascular endothelial growth factor (VEGF). PlGF acts only as a weak mitogen for those cell types possessing receptors for binding (e.g. vascular endothelial cells). At least one high-affinity receptor for PlGF (FLT-1 or VEGF-R1) has been demonstrated in different primary cell types (e.g. human umbilical vein endothelial cells and monocytes). In addition to its action as a weak mitogen it is also a chemoattractant for monocytes and endothelial cells. Three different proteins are generated by differential splicing of the human PlGF gene: PlGF-1 (131aa native chain), PlGF-2 (152aa) and PlGF-3 (203aa). All 3 mitogens are secretable proteins, but PlGF-2 can bind to heparin with high affinity. PlGF is apparently a homodimer, but preparations of PlGF show some heterogeneity on SDS gels depending of the varying degrees of glycosylation. All dimeric forms possess similar biological activities. Heterodimers between VEGF and PlGF are mitogenic for endothelial cells and have strong angiogenic activity in vivo (e.g. in the CAM assay or in the cornea pocket assay). Different cells and tissues (e.g. placenta) express PlGF-1 and PlGF-2 at different rates. A much related protein of PlGF is VEGF with about 53% homology and VEGF-B with similar biological activities.
