The Journal of Immunology, Vol 149, Issue 10 3379-3385, Copyright © 1992 by American Association of Immunologists

ARTICLES

Release of granulocyte-macrophage colony-stimulating factor by alveolar macrophages in the lung of HIV-1-infected patients. A mechanism accounting for macrophage and neutrophil accumulation

C Agostini, L Trentin, R Zambello, P Bulian, C Caenazzo, A Cipriani, P Cadrobbi, S Garbisa and G Semenzato
Padua University School of Medicine, Department of Clinical Medicine, Italy.

In this paper, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lung of patients with HIV-1 infection was evaluated. This cytokine has well recognized effects on granulocyte and macrophage growth and differentiation and plays some role in the mechanisms leading to the accumulation of alveolar macrophages (AM) in patients with interstitial lung disease. Detectable levels of GM-CSF (up to 10 pg/ml) were demonstrated in unconcentrated bronchoalveolar lavage fluid retrieved from HIV-1-seropositive patients, thus suggesting that the GM-CSF is released in vivo in the lung during HIV-1 infection. A statistically significant correlation was demonstrated between the bronchoalveolar lavage concentrations of GM-CSF and the absolute numbers of AM and lung neutrophils. Cell-free supernatants obtained from unstimulated 24-h cultured AM isolated from HIV-1- infected patients contained discrete amounts of GM-CSF, as demonstrated by an immunoenzymatic assay. AM lost the capability of releasing GM-CSF after 72 h of culture, thus suggesting that the production of GM-CSF is not constitutive in AM. After exposition of AM with LPS, the release of GM-CSF and the expression of its mRNA significantly increased with respect to the baseline values; interestingly, the amount of GM-CSF released by LPS-stimulated AM was more than 10-fold higher in HIV-1- infected patients than in healthy subjects. As demonstrated by flow cytometry analysis, more than 70% of freshly isolated AM efficiently bound phycoerythrin-GM-CSF, thus indicating that they express the receptor for GM-CSF. Determination of AM in G1, S, and G2+M by flow cytometry showed that, after 48 h of culture with GM-CSF, 5.5 to 7% of AM entered the proliferative phase of the cell cycle. Taken together, these findings suggest that AM might represent an important source of GM-CSF production in HIV-1 infection. In particular, the hypothesis is formulated that pulmonary opportunists might trigger AM to synthesize GM-CSF in situ. The local overproduction of this cytokine is likely to play a role in the pathogenic events leading to the local proliferation of AM and recruitment of neutrophils in AIDS-associated interstitial lung disease.

This article has been cited by other articles:

				H. KOZIEL, S. KIM, C. REARDON, X. LI, R. GARLAND, P. PINKSTON, and H. KORNFELD Enhanced In Vivo Human Immunodeficiency Virus-1 Replication in the Lungs of Human Immunodeficiency Virus-Infected Persons with Pneumocystis carinii Pneumonia Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 2048 - 2055. [Abstract] [Full Text]

				P. Chen, M. Mayne, C. Power, and A. Nath The Tat Protein of HIV-1 Induces Tumor Necrosis Factor-alpha Production. IMPLICATIONS FOR HIV-1-ASSOCIATED NEUROLOGICAL DISEASES J. Biol. Chem., September 5, 1997; 272(36): 22385 - 22388. [Abstract] [Full Text] [PDF]

				W. C. Hatch, A. R. Freedman, D. M. Boldt-Houle, J. E. Groopman, and E. F. Terwilliger Differential Effects of Interleukin-13 on Cytomegalovirus and Human Immunodeficiency Virus Infection in Human Alveolar Macrophages Blood, May 1, 1997; 89(9): 3443 - 3450. [Abstract] [Full Text] [PDF]