Neutrophil-mediated lung permeability and host defense proteins

Abstract

Neutrophil recruitment to the alveolar space is associated with increased epithelial permeability. The present study investigated in mice whether neutrophil recruitment to the lung leads to accumulation of plasma-derived host defense proteins in the alveolar space and whether respiratory burst contributes to this increase in permeability. Albumin, complement C1q, and IgM were increased in bronchoalveolar lavage (BAL) fluid 6 h after intratracheal LPS challenge. Neutrophil depletion before LPS treatment completely prevented this increase in BAL fluid protein concentration. Respiratory burst was not detected in neutrophils isolated from BAL fluid, and BAL proteins were increased in mice deficient in a key subunit of the respiratory burst apparatus, gp91(phox), similar to wild-type mice. Neutrophil recruitment elicited by intratracheal instillation of the chemokines macrophage inflammatory protein-2 and keratinocyte-derived chemokine was also accompanied by accumulation of albumin, C1q, and IgM. During neutrophil recruitment to the alveolar space, epithelial permeability facilitates delivery of host defense proteins. The observed increase in epithelial permeability requires recruitment of neutrophils, but not activation of the respiratory burst, and occurs with chemokine-induced neutrophil migration independent of LPS exposure.

The non-classical functions of the classical complement pathway recognition subcomponent C1q

“…The association between levels of extracellular gC1qR and increased chemotaxis is mainly due to the fact that gC1qR can simultaneously bind to neutrophils. The role of C1q in chemotaxis is further confirmed through a study in which the lung epithelial permeability was observed to increase following neutrophil recruitment to the site of accumulation of a number of proteins that included albumin, C1q and IgM [26]. C1q has also been implicated in triggering the production of superoxide (O 2 -) by neutrophils [27].…”

Pretreatment with Andrographolide Pills® Attenuates Lipopolysaccharide‐Induced Pulmonary Microcirculatory Disturbance and Acute Lung Injury in Rats

“…ALI at the early stage is characterized by disruption of microvascular endothelium barrier, leakage of protein‐rich fluid into the interstitium and alveolar space, and extensive release of cytokines, and migration of neutrophils . Previous clinical studies showed that the agents directing against only a single insult, such as increased adhesion molecules, TNF‐ α or interleukin ‐1 β release, and ROS production, do not improve the outcome of the patients .…”

HIV Interferes with the Dendritic Cell–T Cell Axis of Macrophage Activation by Shifting Mycobacterium tuberculosis–Specific CD4 T Cells into a Dysfunctional Phenotype

“…DCs were infected with opsonized HIV-1, 1 mg/ml (p24 equivalent/ml), for 2 h prior to infection with opsonized M. tuberculosis (MOI 1). The rationale for opsonizing HIV and M. tuberculosis is that in the host pathogens are naturally opsonized by bodily fluids, and in tissues, during infection (23)(24)(25). Furthermore, HIV uses complement opsonization to enhance infection of immature DCs (26), that is, complement opsonization functioning as an immune evasion mechanism to establish infection in a silent manner (27).…”