Lung pericytes as mediators of inflammation

Abstract

Pericytes are microvascular mural cells that directly contact endothelial cells. They have long been recognized for their roles in vascular development and homeostasis, but more recently have been identified as key mediators of the host response to injury. In this context, pericytes possess a surprising degree of cellular plasticity, behaving dynamically when activated and potentially participating in a range of divergent host responses to injury. Although there has been much interest in the role of pericytes in fibrosis and tissue repair, their involvement in the initial inflammatory process has been understudied and is increasingly appreciated. Pericytes mediate inflammation through leukocyte trafficking and cytokine signaling, respond to pathogen-associated molecular patterns and tissue damage-associated molecular patterns, and may drive vascular inflammation during human SARS-CoV-2 infection. In this review, we highlight the inflammatory phenotype of activated pericytes during organ injury, with an emphasis on novel findings relevant to pulmonary pathophysiology.

Keywords: ARDS; endothelial cells; inflammation; pericyte; sepsis.

Graphical abstract

Figure 1.

DAMPs and PAMPs gain entry into lung interstitium through disrupted alveolar epithelial barrier to activate PRRs on periyctes. Activated lung pericytes express cytokines, chemokines, adhesion molecules, and angioactive mediators to coordinate a local inflammatory response. ANG1, angiopoietin-1; ANGPTL4, angiopoietin-like 4; DAMPs, damage-associated molecular patterns; ICAM, intercellular adhesion molecule; NO, nitric oxide; PAMPs, pathogen-associated molecular patterns; PRRs, pattern recognition receptors; TLR4, Toll-like receptor-4; TNF, tumor necrosis factor; VCAM, vascular cell adhesion molecule. [Image created with BioRender.com and published with permission.]