[bookofjoe]

Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay

ABSTRACT

Wounds in the oral cavity heal much faster than skin lesions. Among other factors, saliva is generally assumed to be of relevance to this feature. Rodent saliva contains large amounts of growth factors such as epidermal growth factor (EGF) and nerve growth factor (NGF). In humans, however, the identity of the involved compounds has remained elusive, especially since EGF and NGF concentrations are ∼100,000 times lower than those in rodent saliva. Using an in vitro model for wound closure, we examined the properties of human saliva and the fractions that were obtained from saliva by high-performance liquid chromotography (HPLC) separation. We identified histatin 1 (Hst1) and histatin 2 (Hst2) as major wound-closing factors in human saliva. In contrast, the d-enantiomer of Hst2 did not induce wound closure, indicating stereospecific activation. Furthermore, histatins were actively internalized by epithelial cells and specifically used the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, thereby enhancing epithelial migration. This study demonstrates that members of the histatin family, which up to now were implicated in the antifungal weaponry of saliva, exert a novel function that likely is relevant for oral wound healing.

Oudhoff, M. J., Bolscher, J. G. M., Nazmi, K., Kalay, H., van 't Hof, W., Nieuw Amerongen, A. V., Veerman, E. C. I.

http://www.fasebj.org/doi/pdf/10.1096/fj.08-112003

[euler_]

Thanks for the information! After reading the abstracts, I still have two question.

1. It sounds like the mechanism for killing cells is very general. Why do histatins not attack somatic cells?

2. Do mouth wounds simply heal faster because the mouth is cleaner?

[bookofjoe]

I'm an anesthesiologist by specialty, with experience as a GP/Family practitioner; the answer to your first question is above my medical pay grade.

In regard to the second, I can say this: in the ER, a human bite is considered FAR more dangerous than a dog bite, because the human mouth has more — and more dangerous — pathogens. The mouth is much dirtier (not cleaner) than skin.

[sndean]

> 1. It sounds like the mechanism for killing cells is very general. Why do histatins not attack somatic cells?

They semi-specifically target a receptor on C. albicans and other pathogens. They're also cationic [1], so they bind anionic lipids in bacteria and mitochondria that aren't found (in large quantities) on the mammalian cell surface.

> 2. Do mouth wounds simply heal faster because the mouth is cleaner?

From that second abstract:

"..histatins were actively internalized by epithelial cells and specifically used the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, thereby enhancing epithelial migration."

It's a relatively simple assay: Just grow a lawn of the skin cells, scrape a line down the middle, and see how quickly the line is filled in (with or without exogenous histatin).

So those peptides tend to do both: kill bacteria and lead to wounds healing faster.

[1] http://aps.unmc.edu/AP/database/query_output.php?ID=00505

[IntronExon]

The cells lining the entire upper GI are exposed to digestive enzymes, and are perforce replaced rapidly and constantly. Until bicarbonate rich bile is added to the mixture in the duodenum, those enzymes (and acids) eat your own cells too. Chemotherapy plays havoc with your GI tract because it selectively kills cells which rapidly divide.

As for histamines, mast cells are designed to respond to them and rupture as part of your inflammatory cycle. They release more cytokines, recruiting neutrophils and in general telling your immune system to attack.

[classichasclass]

Histatins, not histamines.

[IntronExon]

Oops, thanks for the correction!