Schematic diagram of hypothetical pathways for the presence of bovine Hp in milk. There are at least four combined possible pathways for the presence of Hp in milk during mastitis. First, inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) may activate neutrophils and promote them to migrate through the endothelium, subepithelial matrix, and basement membrane of blood and lymph vessels into the infected mammary gland. Neutrophils then pass through the tight junction between the alveolar epithelial cells and enter into the alveolus to secrete cellular Hp (please see review article for more detail [27]) (pathway 1). Second, plasma Hp of hepatic origin mimicking albumin and immunoglobulin [11, 20] is able to directly enter into the epithelial cells via a receptor-mediated process and secrete into alveolus (including endocytosis and exocytosis) (pathway 2). Third, plasma Hp is able to spill into the udder by passive diffusion through a compromised udder/vascular system barrier (pathway 3). Fourth, the mammary epithelial cells are able to endogenously synthesize and express Hp in the alveolus (pathway 4). (A color version of this figure is available at www.vetres.org.)