Surfactant protein A is opsonin in phagocytosis of herpes simplex virus type 1 by rat alveolar macrophages

Abstract

In the present study we used flow cytometry to investigate the phagocytosis of fluorescein isothiocyanate-labeled herpes simplex virus type 1 (FITC-HSV-1) by rat alveolar macrophages and the effects of surfactant protein A (SP-A) on this process. The phagocytosis of FITC-HSV-1 by alveolar macrophages, which was studied as a model for virus phagocytosis in general, was strongly enhanced in the presence of SP-A. The SP-A-mediated phagocytosis was time and concentration dependent, reaching a maximal level after 15 min of incubation and at an SP-A concentration of 5 micrograms/ml. Using a fluorescence quenching technique, we could show that at least 65% of the viruses were indeed internalized by the macrophages. The addition of SP-A to the system was sufficient for the phagocytosis of FITC-HSV-1 by the alveolar macrophages, suggesting that SP-A acts as an opsonin. This hypothesis was further strengthened by the observation that F(ab')2 fragments of immunoglobulin G directed against SP-A could abolish FITC-HSV-1 phagocytosis by alveolar macrophages preincubated with SP-A. Comparing the opsonic capacity of serum and SP-A, SP-A proved to be twice as potent as serum in stimulating phagocytosis of FITC-HSV-1 by alveolar macrophages. Complement factor C1q, which is known to possess a similar collagen-like domain as SP-A, did not stimulate phagocytosis of FITC-HSV-1 by alveolar macrophages nor did it inhibit SP-A-mediated HSV-1 phagocytosis. This study demonstrates that SP-A may play an important role in the antiviral defenses of the lung.

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

“…Surfactant protein A (SP-A), a 34-to 36-kDa glycoprotein, plays a major role in the modulation of innate host defense in the lung (7,16,21,41,48,52). SP-A has been shown to stimulate chemotaxis of macrophages (70), enhance phagocytosis (11,34,44,46,47,50,63), induce generation of reactive oxidants (61), regulate the nitric oxide production (1,23), and influence the proliferation of immune cells (2,38) and the production of proinflammatory cytokines (3,27,37,39,68,69). SP-A can bind to receptors on the macrophage membrane (35).…”

Surfactant protein-A levels increase during Pneumocystis carinii pneumonia in the rat

“…Many of the collectins have been shown to affect phagocytic function. The possibility that SP-A might modulate phagocyte function has been supported by recent in vitro experiments [10][11][12][13][14][15][16], although little is known about its role in vivo. In addition, recent studies from our laboratory have demonstrated that SP-A can also influence immune cell function by stimulating mitogen-induced proliferation and cytokine production [17,18].…”

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

“…We first proposed that SP-A interacted with the glycans of F 2 and enhanced the fusion activity of F protein. It has been reported that SP-A enhanced uptake of HSV [29] and influenza A virus [30] by alveolar macrophages, and a viral and SP-A glyco-conjugate interaction was suggested in these studies. Carbohydrate recognition and opsonization of viruses may be an important role of SP-A in viral clearance.…”