Mediation of entry of human immunodeficiency virus-1 into alveolar macrophages by CD4 without facilitation by surfactant-associated protein-A.
The mechanism of uptake of human immunodeficiency virus-1 (HIV-1) into alveolar macrophages (AM), freshly isolated blood monocytes (MN), and cultured MN (CM) was investigated focusing on the role of CD4 and of surfactant-associated protein A (SP-A). By radioimmunoassay which obviated the problems of auto- and nonspecific fluorescence of more differentiated macrophages, each of the macrophage populations studied expressed CD4. Semiquantitative polymerase chain reaction was performed to assess uptake of HIV-1(JR-FL) into cells. OKT4a (directed against CD4) blocked uptake of HIV-1 into CM, AM, and MN by 67 to 100%. OKT4 (directed against another epitope of CD4) had a smaller and less consistent effect (0-90%), and control antibodies showed minimal effects and only at supersaturating concentrations. SP-A had no effect on uptake of HIV-1 into AM. SP-A also had no consistent effect on production of HIV-1(JR-FL) by AM infected in vitro (p24 antigen ELISA). Thus CD4 is the major receptor for HIV-1 in mononuclear phagocytes, including AM, and SP-A does not modulate entry.
Guay
L A
LA
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106-4984, USA.
Sierra-Madero
J G
JG
Finegan
C K
CK
Rich
E A
EA
D000328:Adult; D000906:Antibodies / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000821:virology*; D008297:Male; D008561:Membrane Fusion / Q000276:immunology*; D009000:Monocytes / Q000821:virology; D010586:Phagocytes / Q000276:immunology; D011510:Proteolipids / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000502:physiology*
D000906:Antibodies; D015704:CD4 Antigens; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants