Acute Lung Injury following Hemorrhagic Shock is governed by macrophage related factors that acts through neutrophils infiltration in a Hemorrhagic Shock rat model

Abstract

Background:- Adult respiratory distress syndrome in hemorrhagic shock is characterized by acute lung injury with a high mortality rate and yet its mechanism is poorly understood. Hemorrhagic shock followed by resuscitation induces a systemic inflammatory response syndrome that results in acute lung injury and other organ dysfunction. This study was designed to assess the possible protective effect of macrophage depletion in hemorrhagic shock-induced acute lung injury.Methods:- 28 adult Albino rats were divided into four groups each containing seven rats: sham group, control group, macrophage depleted group and their vehicle control group. Rats underwent hemorrhagic shock (HS) for 1hr then resuscitated with Ringer’s lactate (1hr) (induced untreated group, HS); The macrophages depletion is done using clodronate disodium carried on liposome as a vehicle, the drug is administered intravenously in dose of 10 units for each 10 g of rat weight, this macrophage depleting agent is given in two doses two days apart and the surgery is done after two days from the second dose, the liposome is administered alone. The lungs were harvested, excised and was fixed in 10% formalin for histological examination. Lung injury was assessed histopathological and neutrophil was stained using immunoflurouscent technique. Results:- There was statistically significant difference between induced untreated (HS) group and sham group (P< 0.05). 100% of the sham group had normal lung injury while 71% of the control group had severe lung injury d up to 85% of macrophage depleted group has only mild lung injury. There is an increase in PMN sequestration in the shock animals and a decrease in the macrophage depleted groups. Shock rat had a 10-fold increase in PMN recruitment vs. sham animals, p<0.05. Rat receiving clodronate had a significant decrease in recruitment vs. control p<0.05.Conclusions:- The current study advances our understanding another level by demonstrating the essential role of the macrophage as initial mediator in secretion an elements that recruits neutrophils in lung during hemorrhagic shock, that will exert their injurious effect through leukotrienes.