A novel experimental model to study leukocyte trafficking to salivary glands

Introduction:

Leukocyte trafficking to the site of inflammation is a fundamental process in the inflammatory response. Inflammatory conditions (e.g., obstructive sialadenitis, in Sjögren's syndrome, or upon radiation) represent the most common pathology of salivary glands in head and neck. The role of leukocytes in this particular context remains poorly understood.

Methods:

Here, we present a novel experimental approach that allows us to study leukocyte responses in the submandibular gland of mice. To this end, we employed multi-channel in vivo microscopy to analyze the intravascular trafficking behavior of fluorescence-labeled leukocyte subsets. Tissue infiltration by these immune cells was assessed by multi-channel flow cytometry analyses of tissue homogenates. Confocal microscopy was used to characterize the expression profiles of adhesion and signaling molecules in the gland's microvasculature.

Results:

Injection of tumor necrosis factor (TNF) into submandibular glands induced surface expression of ICAM-1/CD54 on microvascular endothelial cells as well as tissue infiltration by neutrophils, classical monocytes, and lymphocytes. In vivo microscopy analyses further detected enhanced numbers of intravascularly rolling and adherent leukocytes in TNF-stimulated tissues. These events were significantly diminished upon antibody blockade of ICAM-1/CD54.

Conclusions:

We established a novel experimental model that enables us to characterize the subtype-specific trafficking dynamics of leukocytes in salivary glands as well as to define the underlying molecular mechanisms. This experimental approach might be useful for the development of novel strategies to treat inflammatory salivary gland disorders.

Publication History

Publication Date:
18 April 2018 (online)