Integrin β3 is not critical for neutrophil recruitment in a mouse model of pneumococcal pneumonia

Abstract

Streptococcus pneumoniae is one of the most common causes of bacterial pneumonias in humans. Neutrophil migration into lungs infected with S. pneumoniae is central to the host defense but the mechanisms of neutrophil recruitment, as mediated by S. pneumoniae, into lungs are incompletely understood. Therefore, we have assessed the role of integrin αvβ3 by evaluating its subunit β3 in a mouse model of lung inflammation induced by S. pneumonia. Integrin subunit β3 knockout (β3(-/-)) and wild-type (WT) mice were intratracheally instilled with either S. pneumoniae or saline. Other groups of WT mice were treated intraperitoneally with 25 μg or 50 μg of antibody against integrin β3 or with isotype-matched antibody at 1 h before instillation of S. pneumoniae. Mice were killed 24 h after infection. Flow cytometry confirmed the absence or presence of integrin subunit β3 on peripheral blood neutrophils in β3(-/-) or WT mice, respectively. Neutrophil numbers in bronchoalveolar lavage (BAL) from infected β3(-/-) and WT mice showed no differences. Neutrophil numbers in BAL of infected WT mice treated with β3 antibody were lower compared with those without antibody but similar to those of mice administered isotype-matched antibody. Many neutrophils were present in the perivascular spaces of the lungs in β3(-/-) mice. Lungs from infected β3(-/-) mice had negligible mitogen-activated protein kinase expression compared with those of infected WT mice. Thus, integrin β3 or its heterodimer αvβ3 is not critical for neutrophil migration into lungs infected with S. pneumoniae.

Pneumococcal immune evasion: ZmpC inhibits neutrophil influx

“…Then, the effect of ZmpC was examined in a pneumonia model in C57Bl/6 mice through infection with wild type S. pneumoniae TIGR4 or its isogenic zmpC mutant. As demonstrated before, acute pneumococcal pneumonia is accompanied by massive neutrophil influx 8 h after disease onset (Gauthier et al ., ; Kadioglu et al ., ; Janardhan et al ., ). Here, the intranasal inoculation of mice with wild type TIGR4 resulted in a significantly lower amount of neutrophils recruited to lung lumen compared with the isogenic zmpC mutant (Fig.…”

Regulatory mechanisms of neutrophil migration from the circulation to the airspace

“…VLA-4 also mediates a minor portion of the CD18-independent PMN trafficking to Pneumococcal pneumonia [112]. By contrast, PMN integrin β 3 is reportedly not involved in PMN recruitment to the lungs in Pneumococcal pneumonia [113]. Finally, non-integrin PMN adhesion proteins such as CD47 have also been shown to regulate PMN trafficking to the lung during E. coli pneumonia [114], as further discussed below.…”

Modulation of low-dose ozone and LPS exposed acute mouse lung inflammation by IF1 mediated ATP hydrolysis inhibitor, BTB06584

“…CD61 induces cortical actin reorganization, thus stabilizing focal adhesions ( 22 ). We and others have shown that CD61 knock-out mice, blocking antibodies and peptides like RGD amplify vascular leak, neutrophil recruitment and worsen survival in acute lung injury and sepsis models ( 23 , 24 ). Thus, CD61 is an important regulator of the alveolar barrier.…”