Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages

Oliver Soehnlein, et al. J. Clin. Invest. 118: 3491–3502 (2008)

Speaker: 連國廷                                                   Time: 14:00~15:00, May 27, 2009

Commentator: 謝奇璋 醫師                               Place: Room 601

Abstract:

The polymorphonuclear leukocytes contribute to innate host defense by migrating along chemoattractant gradients to sites of infection and trauma, where they phagocytose opsonized foreign pathogens and release their granule contents in response to phagocytic stimuli and activating factors. The neutrophil granules contain different antimicrobial proteins, proteases and a wide range of membrane-bound receptors for inflammation mediators [1]. It was previously shown that the primary granule proteins, heparin-binding protein (HBP) and human neutrophil peptides (HNPs), could opsonize the bacteria, thereby facilitate bacterial phagocytosis by monocytes/macrophages [2]. However, the authors of this paper found that treatment of monocytes/macrophages with neutrophil granule contents could also enhance the phagocytosis of serum-opsonized bacteria. This result suggested that the neutrophil granule contents could not only directly opsonize the bacteria but also activate the monocyte/macrophage phagocytosis [3]. To identify the major components of neutrophil granule contents that may enhance macrophage phagocytosis, they exposed the macrophages to a variety of purified granule proteins and found that HBP and HNP1–3 markedly enhanced phagocytosis of bacteria opsonized with IgG, but not complements. The enhanced macrophage phagocytosis was resulted from the upregulation of macrophage Fcγ receptors, CD32 and CD64, which bind with IgG. Further, the upregulation of CD32 and CD64 by HBP and HNP1–3 was a result of TNF-α and IFN-γ release by the treated macrophages. They also demonstrated that HBP, but not HNP1–3, activated macrophages via binding with β2 integrins. In conclusion, HBP and HNP1–3 enhanced the macrophage phagocytosis via both the direct opsonization of bacteria and activation of macrophages.

References:

1.      Faurschou M., Borregaard N. 2003. Neutrophil granules and secretory vesicles in inflammation. Microbes Infect. 5: 1317–1327.

2.      Heinzelmann, M., et al. 1998. Heparin binding protein (CAP37) is an opsonin for Staphylococcus aureus and increases phagocytosis in monocytes. Inflammation. 22: 493–507.

3.      Soehnlein O., et al. 2008. Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages. Clin Exp Immunol. 151: 139-145.