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P‐selectin‐dependent platelet‐neutrophil‐interaction (PNI) plays a key role in the development of HCl‐induced acute lung injury (ALI)
Author(s) -
Zarbock Alexander,
Reutershan Joerg,
Singbartl Kai,
Van Aken Hugo,
Ley Klaus
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1258-c
ALI is a syndrome of acute respiratory failure that results from acute pulmonary edema and inflammation. ALI can be caused by extrapulmonary or intrapulmonary injury, such as pneumonia and acid aspiration, and is associated with high mortality. In a murine model of HCl‐induced ALI, we investigated the impact of PNI on pulmonary function and lung injury. After intratracheal HCl‐instillation, mice displayed a severely reduced PaO 2 /FiO 2 (arterial oxygen partial pressure to inspiratory oxygen fraction) ratio after 2h, in contrast to sham mice (sham 639±58mmHg, ALI 223±20mmHg). With a new flow‐cytometry‐based method (Reutershan, Am J Physiol., 289(5):L807, 2005), we demonstrate that HCl‐application leads to intravascular neutrophil (PMN) accumulation from 1.7±0.5 to 4.6±1.6 x 10 6 and transmigration from 0.1±0.05 to 0.5±0.3 x 10 6 PMNs per lung. PMN‐depleted mice were fully protected from HCl‐induced ALI. ALI was accompanied by increased PNI in the systemic circulation. Depletion of platelets with busulfan prior to HCl‐instillation significantly reduced intravascular accumulation and transmigration of PMN (p<0.05) into the lung and significantly improved PaO 2 /FiO 2 ratio to 433±125mmHg. Application of P‐selectin mAb RB40.34 15 min after ALI induction significantly improved PaO 2 /FiO 2 and reduced intravascular accumulation and transmigration of PMN into the lung (p<0.05). Our data suggest that HCl‐induced ALI model is almost completely PMN‐dependent and significantly dependent on P‐selectin‐mediated PNIs. Supported by DFG (ZA428/2‐1) to A.Z. and HL 073361 to K.L.