Sex-specific lung remodeling and inflammation changes in experimental allergic asthma

Abstract

There is evidence that sex and sex hormones influence the severity of asthma. Airway and lung parenchyma remodeling and the relationship of ultrastructural changes to airway responsiveness and inflammation in male, female, and oophorectomized mice (OVX) were analyzed in experimental chronic allergic asthma. Seventy-two BALB/c mice were randomly divided into three groups (n=24/each): male, female, and OVX mice, whose ovaries were removed 7 days before the start of sensitization. Each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, the amount of matrix metalloproteinase (MMP)-2 and MMP-9, and the number of eosinophils and interleukin (IL)-4, IL-5, and transforming growth factor (TGF)-β levels in bronchoalveolar lavage fluid were higher in female than male OVA mice. The response of OVX mice was similar to that of males, except that IL-5 remained higher. Nevertheless, after OVA provocation, airway responsiveness to methacholine was higher in males compared with females and OVX mice. In conclusion, sex influenced the remodeling process, but the mechanisms responsible for airway hyperresponsiveness seemed to differ from those related to remodeling.

Asthma Induction During Development and Adult Lung Function, Behavior and Brain Gene Expression

“…In the current study, airway remodeling, as indicated with collagen buildup, was evident 3 months after completion of asthma symptom exposures. These results suggest that some aspects of lung function (inflammation, mucus, gene expression) persist for a long time after allergen exposure, while aspects related to lung structure (collagen build-up) require a longer time to fully form (Tanaka et al, 2002; Antunes et al, 2010; Salmond et al, 2012). …”

Genomic architecture of asthma differs by sex

“…Genetic association studies of have implicated sex specific effects in INFG [19], TSLP and asthma [26] and CTLA4 with allergic response [27]. Gene expression studies also implicate sex interactions in placental global gene expression in response to asthma [28], IL17BR in allergic response [29] and overall gene expression in humans [30], as well as for asthma related genes in mice [6, 7, 31]. Collectively, these data support a role of sex interaction in the genomics of asthma.…”

“…Young boys are nearly twice as likely to develop asthma as young girls [3, 4]. Animal models also support sex differences in asthma risk with male mice having greater airway hyperresponsiveness than female mice [5] and female mice having higher levels of airway inflammation and pulmonary remodeling than male mice [6, 7]. …”

Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice

“…The volume fraction of collapsed and the normal pulmonary areas, magnitude of bronchoconstriction, and number of mononuclear and polymorphonuclear cells in pulmonary tissue were determined by the point-counting technique [18, 19] across 10 random, noncoincident microscopic fields [14, 20, 21]. Collagen fibers (Picrosirius polarization method) were quantified in airways and alveolar septa using Image-Pro Plus 6.0 software [13, 22]. …”