Pressure is proinflammatory in lung venular capillaries
Wolfgang M. Kuebler, Xiaoyou Ying, Baljit Singh, Andrew C. Issekutz, Jahar Bhattacharya
Wolfgang M. Kuebler, Xiaoyou Ying, Baljit Singh, Andrew C. Issekutz, Jahar Bhattacharya
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Article

Pressure is proinflammatory in lung venular capillaries

Abstract

Endothelial responses may contribute importantly to the pathology of high vascular pressure. In lung venular capillaries, we determined endothelial [Ca2+]i by the fura-2 ratioing method and fusion pore formation by quantifying the fluorescence of FM1-43. Pressure elevation increased endothelial [Ca2+]i. Concomitantly evoked exocytotic events were evident in a novel spatial-temporal pattern of fusion pore formation. Fusion pores formed predominantly at vascular branch points and colocalized with the expression of P-selectin. Blockade of mechanogated Ca2+ channels inhibited these responses, identifying entry of external Ca2+ as the critical triggering mechanism. These endothelial responses point to a proinflammatory effect of high vascular pressure that may be relevant in the pathogenesis of pressure-induced lung disease.

Authors

Wolfgang M. Kuebler, Xiaoyou Ying, Baljit Singh, Andrew C. Issekutz, Jahar Bhattacharya

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Fusion pore formation in lung venular capillaries. (a) Images of a singl...
Fusion pore formation in lung venular capillaries. (a) Images of a single capillary taken at different PLA. PLA of 5 cmH2O. Images are before (top) and after (bottom) pressure elevation was obtained after 5 minutes of FM1-43 infusion. PLA of 20 cmH2O. Images were obtained at different time points after start of dye infusion. Color code shows fluorescence intensities. Capillary branch point (arrowheads) and midsegmental (arrow) locations are marked. Vessel margins are depicted by line sketches. Replicated in 8 capillaries. (b) After 30 minutes at PLA of 20 cmH2O, FM1-43 was infused into a lung venular capillary (horizontal bar) and then washed out by the blood flow (arrow). Shown is capillary fluorescence per unit surface area. Replicated in 8 capillaries. (c) Capillary fluorescence was quantified in pixels 5 × 5 μm2, at midsegmental and branch point locations after 5 minutes of FM1-43 infusion. Data were obtained at PLA of 5 cmH2O and after 30 minutes of PLA increase to 20 cmH2O in control (n = 8) and gadolinium-treated (n = 4) lungs. Gadolinium did not increase fluorescence above control at PLA of 5 cmH2O (not shown). *P < 0.05 vs. PLA of 5 cmH2O.