Surfactant protein A differentially regulates peripheral and inflammatory neutrophil chemotaxis

Abstract

Surfactant protein A (SP-A), a pulmonary lectin, plays an important role in regulating innate immune cell function. Besides accelerating pathogen clearance by pulmonary phagocytes, SP-A also stimulates alveolar macrophage chemotaxis and directed actin polymerization. We hypothesized that SP-A would also stimulate neutrophil chemotaxis. With the use of a Boyden chamber assay, we found that SP-A (0.5-25 microg/ml) did not stimulate chemotaxis of rat peripheral neutrophils or inflammatory bronchoalveolar lavage (BAL) neutrophils isolated from LPS-treated lungs. However, SP-A affected neutrophil chemotaxis toward the bacterial peptide formyl-met-leu-phe (fMLP). Surprisingly, the effect was different for the two neutrophil populations: SP-A reduced peripheral neutrophil chemotaxis toward fMLP (49 +/- 5% fMLP alone) and enhanced inflammatory BAL neutrophil chemotaxis (277 +/- 48% fMLP alone). This differential effect was not seen for the homologous proteins mannose binding lectin and complement protein 1q but was recapitulated by type IV collagen. SP-A bound both neutrophil populations comparably and did not alter formyl peptide binding. These data support a role for SP-A in regulating neutrophil migration in pulmonary tissue.

Identification of the Surfactant Protein A Receptor 210 as the Unconventional Myosin 18A

“…Adelstein and co-workers (86) have already identified a third nonmuscle myosin II family member, MyoIIC. Mechanistically, the aforementioned intracellular functions of MyoIIA are related to a variety of functional activities of SP-A on cell motility and migration (25,26), lipid secretion, lymphocyte proliferation (46), and phagocytosis (13,17,21,22,82).…”

Surfactant protein A regulates IgG-mediated phagocytosis in inflammatory neutrophils

“…The lack of effect of SP-A in fMLP-or PMA-induced production of ROS and the small effect on fMLP-induced F-actin polymerization indicate that SP-A is not having a generalized activation effect that merely enhances all inflammatory functions measured. We have shown that SP-A enhances fMLP-and macrophage inflammatory protein-2-induced chemotaxis in inflammatory neutrophils (23). The finding that SP-A enhanced IgG-mediated phagocytosis when preincubated with neutrophils suggests that SP-A may have a direct effect on neutrophil phagocytosis of particles opsonized by IgG.…”

“…Inflammatory neutrophils were obtained as previously described (23). In brief, male Sprague-Dawley rats, 250 -400 g, from Taconic Farms (Germantown, NY) were instilled intratracheally with O26:B6 LPS (100 g/kg in 0.9% saline) to induce acute inflammation in the lungs.…”

“…For example, Schagat et al (23) compared the effects of SP-A on functions of peripheral, unactivated neutrophils from the blood and on inflammatory neutrophils lavaged from inflamed rat lungs. In contrast to its effects on macrophages, SP-A alone was unable to elicit chemotaxis in either peripheral or inflammatory neutrophils.…”

Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

“…Inhibitory effects of SP-A include decreased cytokine expression and nitric oxide production in mouse and rat macrophages pretreated with LPS (3,11,51). Moreover, SP-A appears to regulate activities of cells other than those of the monocyte/macrophage lineage (17,70) as well as to modulate components of adaptive immunity by exhibiting mainly an inhibitory effect. With regard to its role in adaptive immunity, SP-A has been shown to inhibit basal and LPS-mediated expression of the major histocompatibility complex class II and CD86 molecules in murine dendritic cells (DC) as well as DC allostimulation of T cells (15).…”