Mechanism of Pneumocystis carinii attachment to cultured rat alveolar macrophages.

Abstract

Pneumocystis carinji (PC) pneumonia begins as an intra-alveolar process resulting in injury to the alveolar epithelium with subsequent invasion of the lung interstitium. The clearance of PC organisms from the alveolar space is a critical function of alveolar macrophages (AM), the resident alveolar phagocytic cells. In this study the mechanism of PC attachment' to AM was determined using 51Cr-labeled organisms, with PC attachment reaching a maximum of 18.9±2.5% after 4 h. Attachment was significantly decreased'by preincubation of the AM with' a monoclonal anti-fibronectin antibody directed againstthe cell attachment site of fibronectin (from 17.8±2.2% to 8.3±1.0%, P <'0.01), or by addition of the fibronectin cell binding site analogue Arg-Gly-Asp-Ser (RGDS) (from 18.1±2.3% to 2.9±0.8%, P < 0.01). An anti-fibronectin monoclonal antibody directed against the heparin binding domain of fibronectin had no effect on PC attachment. Addition of the specific calcium ion chelating agent EGTA to the culture media similarly decreased attachment from 16.9±2.0% to 5.1±1.1% (P < 0.01). Fibronectin-mediated attachment of PC to AM did not result'in phagocytosis of the organisms by the AM as determined by chemiluminescence measurements. Therefore, the data indicate that PC attachment to AM is a calcium-dependent process mediated by the cell binding domain of fibronectin which does not trigger a phagocytic response by the

Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages.

“…The difference between these two determinations provides an estimate of phagocytosis. To evaluate the role of SP-D in binding and phagocytosis of P. carinii by macrophages, we compared the interaction of freshly isolated P. carinii, EDTA-treated organisms, and EDTA-treated P. carinii with additional SP-D. As an independent confirmation of the effectiveness of these agents in impairing phagocytosis, we and others have observed previously that adenosine and homocysteine thiolactone effectively inhibit the phagocytosis of opsonized zymosan particles by alveolar macrophages using the luminol-dependent chemiluminescence method (61).…”

“…In particular, the adhesive glycoprotein fibronectin has been implicated in P. carindi attachment to cultured lung epithelial cells and macrophages (49,61). Interestingly, like SP-D, fibronectin enhances the attachment of P. carinii to alveolar macrophages, but does not augment phagocytosis of the organisms (61).…”

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

“…The role of other receptors implicated in the AM recognition of Pneumocystis, including fibronectin (Pottratz and Martin, 1990) and immunoglobulin receptors (Masur and Jones, 1978;von Behren and Pesanti, 1978) were not specifically investigated. The observed Cdc42 and Rac phosphorylation in response to IgG-opsonized Pneumocystis in AMs with targeted gene silencing of the mannose receptor suggests that the Fc␥R pathway was intact.…”

Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation.

“…The specific role and likely contribution of other molecules implicated in the interaction of P. carinii with macrophages, including F c (14,18), fibronectin (62), and vitronectin (63) receptors, and the role of SP-A (64) and SP-D (65) were not examined. Although all cells were exposed to FCS, contaminating proteins and macromolecules derived from rat and mink cells which may influence P. carinii binding and phagocytosis need to be considered as possible confounding factors.…”