- How are you?
- Fine, and you?
- How's it going?
- OK. How's it going with you?"
(something) is up means something is happening. "What's up?" is just another way of saying "What's happening?" / "What's going on (that might interest me the speaker)?"
Sth is up意思是sth is happening（某事）发生。“What's up?”其实是“What's happening?（发生了什么）”，“What's going on(能勾起发问者兴趣的事情)？”的另一种形式。
That is an expression that has about as much meaningfulness as "How are you?" or "How's it going?"
这是一个和"How are you?"、"How's it going?" 基本上有相同意义的表达。
All, including "What's up?" are used as greetings.
It has however fallen into common usage both in the US and UK.
-Not much / nothing, how about with you?
- Not too much, just trying to get my car clean.
- Just trying to get a little exercise in. What’s up with you?