Sterile kidney tissue injury induces neutrophil swarming in lung alveolar capillaries

Abstract

AbstractSterile tissue injury, such as by acute kidney injury, is common in the clinic and frequently associated with respiratory compromise and hypoxemia. We previously described signaling components released by the injured kidney that drive a remote inflammatory response in the lung. How this caused the resultant hypoxemia remained unclear. Here, we report that sterile kidney tissue injury induces rapid intravascular “neutrophil train” formation in lung capillaries, a novel form of neutrophil swarming. Rapid swarming is enhanced by decreased deformability of circulating neutrophils that impedes their lung capillary passage. Classical lung monocytes are required for neutrophil train formation and release CXCL2 to attract and retain stiffened neutrophils in lung capillaries which reduces capillary perfusion. We thus discovered a novel feature of kidney-lung crosstalk after sterile kidney tissue injury, capillary perfusion deficits that lead to reduced oxygenation despite proper alveolar function and ventilation, unlike in infectious inflammatory lung processes, such as bacterial pneumonia.