Upregulation of expression of platelet-derived growth factor and its receptor in pneumonia associated with SHIV-infected macaques.
BACKGROUND
HIV-associated pulmonary disorders are the most frequent cause of AIDS-related deaths. Rhesus macaques infected with SIV-HIV (SHIV) recapitulate the human HIV-1 lung disease and provide an excellent working model to study the pathogenesis of the human syndrome. Lungs of macaques with SHIV-associated pneumonia have pathology involving macrophage and T cell infiltration that is often accompanied with concurrent opportunistic infections.


OBJECTIVE
To explore the relationship between SHIV-associated respiratory disease and the expression of platelet-derived growth factor (PDGF) B chain (PDGF-B) and its cognate receptors, PDGF-Ralpha and PDGF-Rbeta, which have been implicated in chronic inflammatory processes.


METHODS
Lung tissues from 10 SHIV-infected rhesus macaques were evaluated for pathological changes and correlation of these lesions with PDGF-B/PDGF-R expression by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.


RESULTS
Virus-associated pneumonia was associated with virus replication in macrophages in the lungs, enhanced recruitment of macrophages and mononuclear cells into the organ, and, occasionally, fibrosis. These changes were accompanied by upregulation of PDGF-B and its cognate receptors in the diseased tissue. Confocal microscopy identified SHIV-infected macrophages as one of the major cell types expressing PDGF-B and PDGF-Ralpha/beta in the affected lungs.


CONCLUSIONS
These results suggest that PDGF and its cognate receptors play a critical role in the pathogenesis of pulmonary disease associated with this virus.
Dhillon
Navneet K
NK
Department of Microbiology, Immunology and Molecular Genetics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Sui
Yongjun
Y
Pinson
David
D
Li
Shanping
S
Dhillon
Sukhbir
S
Tawfik
Ossama
O
Callen
Shannon
S
Nemon
Olga
O
Narayan
Opendra
O
Buch
Shilpa
S
D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D015497:HIV-1 / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000821:virology; D008251:Macaca; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000821:virology; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011024:Pneumonia, Viral / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D015854:Up-Regulation; D014779:Virus Replication
D010980:Platelet Membrane Glycoproteins; D020574:Proto-Oncogene Proteins c-sis; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor