The Role And Mechanism Of P-selectin Glycoprotein Ligand-1 In Acid Aspiration-induced Lung Injury In Mice

Objective To investigate the role and its possible mechanism of P-selectin glycoprotein ligand-1(PSGL-1)in hydrochloric acid-induced acute lung injury(ALI)in mice.Methods 30 male Wild-type mice(WT)and 30 male PSGL-1 knockout mice(PSGL-1-/-)were randomly subjected to normal saline(NS)or hydrochloric acid(HCl)instilled challenged group.Mice were intratracheally instilled of NS or HCl(1 ?l/g weight)into the left lung with a catheter.After 2 hours,respiratory function(Penh),partial pressure of oxygen(Pa O2),and carbon dioxide(Pa CO2)in the arteria blood were analyzed.The wet to dry weight ratio(W/D)of left lung and total protein concentration in bronchoalveolar lavage fluid(BALF)were measured.The number of leukocytes in BALF was counted.Targeted lung tissue was processed for further hematoxylin and eosin(HE)to observe the pathological change.Immunohistochemistry was utilized to analyze the inflammatory cells infiltration in the process of ALI.The adapted ELISA was used to determine the concentration of interleukin-6(IL-6)and interleukin-1 ?(IL-1?)in left lung tissue.Meanwhile,the expression of nuclear transcription factor(NF-?B),I?Ba and p-I?Ba in lung tissue was detected by Western blot.Results PSGL-1 knockout mice showed significantly lower in Penh(4.77±1.22)and Pa CO2 [(63.72±3.92)mm Hg,1mm Hg=0.133 k Pa] compared with WT mice in Penh(5.80±0.84)and Pa CO2 [(74.37±7.38)mm Hg] after HCl stimulation(p<0.05).However,the Pa O2[(81.00±7.13)mm Hg] in PSGL-1-/-mice was higher than that [(62.75±13.62)mm Hg] in WT mice(p<0.05).The W/D ratio of lung(4.86±0.15),protein concentration(3.71±0.64)and total leukocyte count(13.00±2.18)in BALF were significantly lower in PSGL-1-/-mice challenged with HCl than those correspongding values(5.22±0.20,4.74±0.98,49.42±3.35)in WT mice(p<0.05 respectively).Worthy of noting that,the protein expression of IL-6,IL-1?,p65 and p-I?Ba(33.84±5.89,38.15±7.50,1.20±0.40,0.33±0.05)in PSGL-1-/-mice was much lower than those(58.86±5.21,47.82±1.54,2.43±0.54,0.52±0.14)in WT mice after HCl inhalation(p<0.05 respectively),while the I?Ba expression(0.91±0.18)was much higher than that(0.57±0.22)in WT mice(p<0.05).More numbers of neutrophils and macrophages infiltration was found in the lung of WT than PSGL-1-/-mice challenged with HCl.However,the difference of above values between WT mice and PSGL-1-/-mice instilled with NS was not found and all of them were significantly lower than the correspongding HCl group except I?Ba(p<0.05).Conclusion PSGL-1 may play an important role in the development of ALI induced by HCl and inflammation via the NF-?B signaling pathway.