Strain-specific differences in perivascular inflammation in lungs in two murine models of allergic airway inflammation

Abstract

Histological data show perivascular recruitment of inflammatory cells in lung inflammation. However, the process of perivascular inflammation is yet-to-be characterized in any systematic manner at cell and molecular levels. Therefore, we investigated impact of genetic background on perivascular inflammation in acute or chronic airway inflammation in different strains of mice. Further, to address molecular mechanisms of perivascular inflammation, we examined immunohistochemical expression of vascular adhesion protein-1 (VAP-1) in chronic airway inflammation. Histological scoring revealed time and strain specific differences in perivascular recruitment of inflammatory cells in chronic and acute airway inflammation (P < 0.05). The data show that A/J strain is significantly more susceptible for perivascular inflammation followed by BALB/c and C57BL/6, while C3H/HeJ strain showed no perivascular accumulation of inflammatory cells. Of the two strains examined for perivascular inflammation in acute airway inflammation, BALB/c showed more accumulation of inflammatory cells compared to C57BL/c. VAP-1 expression occurred in the endothelium of pulmonary arteries but not in alveolar septa or airways in the control as well as challenged mice. In the inflamed lungs from A/J mice, the VAP-1 staining in pulmonary arteries was more intense compared to the other strains. VAP-1 staining was generally observed throughout the pulmonary arterial wall in chronic lung inflammation. These data show that periarterial inflammation is influenced by the genetic background, and may be partially regulated by VAP-1.

Fig. 1

Histology analyses of H&E stained sections: Lung sections graded as (a) normal, (b) Grade I, (c) Grade II and (d) Grade III. *Lumen of an artery. Original magnification: ×20

Fig. 2

Histological scores of perivascular recruitment of inflammatory cells in chronic allergic airway inflammation. Groups bearing superscripts (for example a) were significantly (P < 0·05) different from the groups bearing superscripts other than ‘a’ (for example b or c) while the groups with similar superscripts did not differ significantly.

Fig. 3

Histological scores of perivascular recruitment of inflammatory cells in acute allergic airway inflammation. Groups bearing superscripts (for example a) were significantly (P < 0·05) different from the groups bearing superscripts other than ‘a’ (for example b) while the groups with similar superscripts did not differ significantly.

Fig. 4

VAP-1 immunostaining: Lung section incubated without primary antibody but with secondary antibody (a) show no staining while CD3 antibody stains (asterisks) peribronchial lymphocytes (b). VAP-1 staining (arrows) in lung section from a normal A/J mouse (c) and those challenged for (d) 4 weeks and (e) 8 weeks. (f) Lung section from a BALB/c mouse challenged for 8 weeks and shows VAP-1 staining in the wall of pulmonary artery. Original magnification: a ×10; b, c and e ×20; d and f ×40