Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways

Human lung fibroblasts represent important targets for the biologic activities of bradykinin (BK). We have identified multiple mechanisms in these cells which may extend their potential for BK receptor responsiveness, particularly with regard to generation of arachidonate metabolites. These fibroblasts can constitutively express B2 and B1 BK receptors concurrently, both coupled to the pathway for arachidonate metabolism resulting in generation of PGE2 and the potent vasoactive lipid mediator Thromboxane A2. Although expression patterns for B2 and B1 receptors have classically been regarded as 'constitutive' and 'inducible', respectively, we demonstrate that in human lung fibroblasts both can be expressed spontaneously at equivalent biologic activity levels without selective induction by other mediators. Concurrent B2/B1 receptor expression extends the scope of fibroblast response potential to both BK and des-Arg9-BK in the same time frame. We have identified additional short-term and long-term cellular events, involving both protein kinase pathways through which BK receptors act and those which act upon BK receptors, that result in enhanced BK receptor response potential. These properties of BK receptors may affect whether fibroblast behaviors maintain controlled activities of normal homeostasis or foster escalating cellular responses which may influence the progression of certain human disease states.