The data overall suggest that the amount of specific IgG antibody alone does not account for differences in the TMA-GPSA-induced response seen with age and gender. in the lung cells increased only in immature animals. IgG antibodies differed between organizations but did not account for variations in cell infiltration. C3a correlated with the degree of cell infiltration in all organizations except adult females. Conclusions TMA-induced neutrophilia differs with age. TMA-induced changes in eosinophils and macrophages did not vary with age or gender. The relationship between match activation and swelling in adult females differs from that in the additional organizations, suggesting mediators of the response may switch with age and gender. Effects of Araloside V age and gender need to be regarded as in animal models of the sensitive response. Keywords: Asthma, occupational; Swelling; Trimellitic anhydride; Acid anhydrides; Eosinophils; Match; C3a Intro Trimellitic anhydride (TMA), used in the paints and plastics industries, is one of many low-molecular-weight chemicals known to cause occupational asthma. Earlier studies by us [1] as well as others [2C4] have characterized a guinea pig model of TMA-induced asthma. Guinea pigs sensitized by intradermal injection of TMA in corn oil and challenged by intratracheal instillation of TMA conjugated to guinea pig serum albumin (TMA-GPSA) respond with immediate bronchoconstriction, microvascular leakage of proteins and infiltration of inflammatory cells into the lung, including significant eosinophilia. These and additional studies of TMA-induced respiratory disease in the guinea pig have used Hartley or Dunkin-Hartley guinea pigs weighing approximately 300 g (estimated age of 21C28 days) at the time of sensitization [observe 5C10]. Guinea pigs this size are not yet sexually adult, but have been used to study effects of an occupational allergen where exposure to adults is definitely of main concern. Certainly in humans the incidence of asthma varies with age and gender [11C13]. Arakawa et al. [2] studying the effects of TMA in guinea pigs speculated that variations in airway resistance and plasma exudation observed over time were due to maturation of the animals. However, the effects of age and gender within the guinea pig sensitive response induced by TMA and additional low-molecular-weight chemicals have received little consideration. The effects of age and gender on bronchoconstriction and vascular permeability induced by inflammatory mediators and the antigen ovalbumin have been studied. However, consistent patterns of the effects have not emerged. The effects of leukotriene D4 [14] and histamine [15] in contracting isolated respiratory cells, and leukotriene D4 and a thromboxane A2 mimetic in inducing changes in lung resistance [16] are more pronounced in immature guinea pigs than in adult animals. By contrast, ovalbumin- and histamine-induced bronchoconstriction are more pronounced in adult guinea pigs [17, 18]. Histamine-induced plasma exudation in the lung is definitely more pronounced in immature guinea pigs than in mature animals [18], whereas ovalbumin- or Araloside V eicosanoid-induced plasma exudation is definitely more pronounced in mature guinea pigs [16, 17]. Bradykinin, neurokinin A and compound P are more effective at increasing airway resistance and extravasation of Evans blue dye in adult guinea pigs compared to immature animals [19, 20]. With regard to gender variations, Duncan and Douglas [14] reported the potency of leukotriene D4 Araloside V in contracting respiratory tissue decreased with maturation to a greater extent in female than male animals. Although these studies provide some understanding of the effects of age and gender with respect to changes in bronchoconstriction and vascular permeability in the guinea pig, the effects of age and gender on antigen-induced cell infiltration are relatively unexplored. In the present study we hypothesize that TMA-induced cellular infiltration into the guinea pig lung is similar in animals of both genders, whether sensitized to TMA when sexually immature, as offers historically been carried out, or sensitized after reaching sexual maturity. To test this hypothesis, TMA-induced cellular infiltration into the lung and bronchoalveolar lavage Mouse monoclonal to EPO fluid (BAL) was examined 24 h after intratracheal instillation of TMA-GPSA in both female and male guinea pigs sensitized to TMA when either sexually immature or after reaching sexual maturity. Red blood cells, an indication of lung injury, and total protein in the BAL were also measured. To determine if variations in cell infiltration could be accounted for by variations in sensitization, TMA-specific IgG1 and IgG2 antibodies in plasma were measured. Previously we had demonstrated that activation of the match system played a role in TMA-induced cellular infiltration in immature guinea pigs [1], and that the concentration of the match activation product C3a correlated with the degree of TMA-induced cell infiltration in immature woman guinea pigs [21]. Consequently, C3a was measured to determine if variations in cell infiltration might be attributed to variations in mediator launch. Materials and Methods TMA Sensitization and Challenge All animal.