Brain macrophage surface marker expression with HIV-1 infection and drug abuse: a preliminary study.
OBJECTIVE
To determine the heterogeneity of surface marker expression of macrophages in the temporal lobe of patients who died with AIDS who were also Drug Abusers (DAs). We studied the expression of macrophage surface markers CD11c, CD14, CD68, and HLA-DR and T cell surface markers CD4, and CD8.


BACKGROUND
The macrophage is the prime locus for HIV-1-associated pathology, is the most frequently infected cell in the brain, and has the highest virus load compared to other cells. We previously described the heterogeneity of macrophage surface marker expression and performed morphometric analysis in peripheral nerves of patients who died from AIDS compared to HIV-1 negative individuals. We showed that the HIV-related neuropathy in AIDS is a multifocal process. It is similarly important to determine the expression of macrophage surface markers in brain. Temporal lobe tissue was selected for this preliminary study because we previously found elevated HIV-1 proviral DNA load and inflammatory processes in this neuroanatomic location for subjects who died with AIDS. There is a high prevalence of Drug Abuse in Miami, Florida, associated with AIDS that may interactively affect HIV-associated pathology.


METHODS
Temporal lobe tissue was examined from 17 HIV-1-seropositive patients (4 with Drug Abuse and 13 without Drug Abuse) and 11 HIV-seronegative individuals (5 with Drug Abuse and 6 without Drug Abuse). Standard immunohistochemistry utilized alkaline phosphatase conjugate secondary antibody and fuchsin substrate.


RESULTS
We found that HIV-1 infection and the interaction of HIV-1 infection and Drug Abuse produced changes in macrophage surface marker expression. Macrophage surface markers, CD11c, CD14, CD68, and HLA-DR, and T-cell marker CD4 were increased with statistical significance due to HIV-1 infection (all p < .001) whereas CD8 remained unchanged. Changes due to Drug Abuse alone were not significant. Interaction of Drug Abuse and HIV-infected individuals showed increased expression of CD68 (p = .011), HLA-DR (p = .001), CD4 (p = .027), and CD8 (p = .016).


CONCLUSIONS
Drug Abuse and HIV-1 infection are factors that differentially and interactively result in multiple macrophages surface marker effects. In HIV-1 infected individuals, Drug Abuse stimulates surface marker expression. Since brain macrophage surface makers do not change uniformly as a result of Drug Abuse and HIV infection, these cells may be heterogeneous and contain sub-types (sub-sets). It remains to be determined which macrophage sub-types may be most pathognomic for pathology.
Shapshak
Paul
P
Department of Psychiatry and Behavioral Sciences, Comprehensive Drug Research Center, University of Miami School of Medicine, FL 33136, USA. pshapsha@med.miami.edu
Stewart
Renée V
RV
Rodriguez de la Vega
Pura
P
Dominguez
Boanerges
B
Fujimura
Robert
R
Segal
David M
DM
Sun
Nora C J
NC
Delgado
Silvia
S
Petito
Carol
C
D015526:AIDS Dementia Complex / Q000150:complications / Q000276:immunology / Q000473:pathology*; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D039521:CD11c Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002452:Cell Count; D005260:Female; D015497:HIV-1; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019966:Substance-Related Disorders / Q000150:complications / Q000276:immunology / Q000473:pathology*; D013702:Temporal Lobe / Q000276:immunology / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D039521:CD11c Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; C067980:CD68 antigen, human; D000097382:CD68 Molecule